CHARACTERIZATION OF A MAJOR OBESITY LOCUS

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DESCRIPTION (provided by applicant): Obesity is reaching epidemic proportions in the U.S. with over 60% of Americans being either obese or overweight. Obesity has a strong genetic component, however, relatively little is known regarding the specific identity of genes with common alleles influencing obesity. To characterize natural genetic variation influencing obesity I propose to study the BCQ-hg/hg congenic strain. BC9-hg/hg mice are congenic for CAST/EiJ chromosome 9 alleles on a C57B\/6J-hg/hg background. BC9-hg/hg females are 57% and males are 30% more obese than control mice, hg is a deletion on mouse chromosome 10 leading to a 30-50% increase in body size and evidence suggests that hg is required for obesity in BCQ-hg/hg mice. To better understand the nature of BCQ-hg/hg obesity I have outlined three specific aims. Aim 1 measures the effect of age and diet on BCQ-hg/hg obesity and will determine if obesity is dependent on the presence of hg. Aim 2 uses a congenic-derived F2 population to narrow the genomic interval harboring the obesity QTL. Lastly, aim 3 uses a genetical genomics approach to map eQTL for genes within the congenic interval. Data from these aims will enhance our understanding of the genetics and physiology of obesity.